DESCRIPTION: (Adapted from the application) Veins play an important role in cardiovascular homeostasis by modulating venous return, cardiac preload, cardiac output and myocardial oxygen demand. Venous function is controlled, at least in part, via the arterial baroreceptor reflexes. However, cardiac reflex control of veins has received comparatively little study. Studies in dogs suggest that cardiac vagal afferent pathways cause venodilation and a reduction in cardiac filling. Moreover, changes in venous tone are involved in the cardiovascular responses to coronary ischemia, congestive heart failure and myocardial infarction. Thus, cardiac reflex control of venous tone may play an important role in cardiovascular homeostasis. In addition, estrogen is thought to exert cardioprotective effects at least in part via direct effects on vascular smooth muscle, via potentiation of the nitric oxide system, via interaction with cardiovascular reflexes or via effects in the central nervous system. Recent studies suggest that cardiac reflex control of sympathetic nerve activity is enhanced in female rats and that female gender protects the heart from ischemia. Estrogen modulation of reflex function may serve to protect the ischemic heart by lowering venous return, preload and myocardial oxygen demand. The proposed research will address the general hypothesis that: Estrogen modulates cardiac afferent reflex control of venous tone in conscious rats. The specific aims will be test three predictions of this hypothesis: I) Estrogen attenuates cardiac pressor afferent mediated venoconstriction. II) Estrogen enhances cardiac depressor afferent induced venodilation. III) Estrogen modulates cardiac afferent reflex control of venous tone via an effect in the PVN. These working hypotheses will be tested by measuring mean arterial pressure, heart rate and mean circulatory filling pressure (MCFP), an index of integrated venomotor tone in conscious rats. These variables will be monitored during stimulation of cardiac pressor and depressor afferents by pericardial injection of bradykinin and serotonin respectively. Comparing responses in male and female rats subjected to sham surgery, gonadectomy or gonadectomy+estrogen replacement will assess the modulatory role of estrogen. The role of the PVN will be studied via lesion and microinjection experiments. In order to determine if nitric oxide is involved in the estrogenic effects, responses will be obtained before and after blockade of nitric oxide synthase. These studies are expected to demonstrate that cardiac afferent control of peripheral venomotor tone is modulated by estrogen via an interaction with nitric oxide.